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    • 55. 发明申请
    • IMMEDIATE RELEASE DRUG FORMULATION COMBINING OPIOID AND NONOPIOID ANALGESICS WITH ABUSE DETERRENCE AND OVERDOSE PROTECTION
    • 立即释放药物制剂与阿片类药物和非甾体类镇痛药物的不良反应和过量保护
    • WO2017192608A1
    • 2017-11-09
    • PCT/US2017/030667
    • 2017-05-02
    • KASHIV PHARMA LLC
    • VAKA, Siva, Ram KiranMEGHPARA, KanjiDESAI, DipenPHUAPRADIT, WantaneeSHAH, Navnit, H.THONGSUKMAK, Atsawin
    • A61K9/16A61K9/20A61K9/48A61K9/50A61K31/167A61K31/485
    • A61K9/5073A61K9/1611A61K9/1623A61K9/1635A61K9/1641A61K9/1652A61K9/2081A61K9/2086A61K9/48A61K9/5026A61K9/5042A61K9/5047A61K9/5084A61K31/167A61K31/485
    • The present disclosure provides solid immediate release (IR) dosage forms, including particulate and multi-particulate dosage forms, with abuse deterrent and overdose protection characteristics. In certain embodiments, the dosage form is multi¬ particulate, comprising: a first population of particulates comprising a therapeutically effective amount of at least one opioid embedded in a polymer matrix, an optional seal coat, a functional coat layer(s), and an over coat, wherein the functional coat layer(s) comprises a nonionic water-insoluble polymer, and a cationic polymer that dissolves at a pH of less than about 5; a second population of particulates comprising a therapeutically effective amount of acetaminophen (APAP) embedded in a polymer matrix, an optional seal coat, a functional coat layer(s), and an over coat, wherein the functional coat layer(s) comprises a cationic polymer that dissolves at a pH of less than about 5 and an optional nonionic water-insoluble polymer; and a third population of particulates comprising an alkaline agent, and an optional pH-stabilizing agent, wherein the alkaline agent raises the gastric pH when three or more dosage units are ingested, and the pH-stabilizing agent maintains the elevated pH. The dosage forms, including particulate and multi-particulate dosage forms, are designed to accomplish the desired combination of analgesia, abuse deterrence, and overdose protection.
    • 本公开提供了具有滥用威慑和过量保护特征的固体立即释放(IR)剂型,包括颗粒剂和多颗粒剂型。 在某些实施方案中,剂型是多&不; 其包含:第一群粒子,其包含治疗有效量的嵌入聚合物基质中的至少一种阿片样物质,任选的密封包衣,功能包衣层和外包衣,其中功能包衣层 )包含非离子型水不溶性聚合物和在小于约5的pH下溶解的阳离子型聚合物; 包含嵌入聚合物基质中的治疗有效量的对乙酰氨基酚(APAP),任选的密封包衣,功能包衣层和外包衣的第二群颗粒,其中所述功能包衣层包含阳离子 在小于约5的pH下溶解的聚合物和任选的非离子型水不溶性聚合物; 以及第三群颗粒,其包含碱性试剂和任选的pH稳定剂,其中当摄入三个或更多个剂量单位时,所述碱性试剂提高胃的pH,并且所述pH稳定剂保持提高的pH。 包括颗粒剂和多颗粒剂型在内的剂型设计用于实现镇痛,滥用威慑和过量保护的所需组合。
    • 60. 发明申请
    • COCRYSTALS OF NALOXONE AND NALTREXONE
    • 纳洛酮和NALTREXONE的共晶体
    • WO2017053936A8
    • 2017-04-27
    • PCT/US2016053695
    • 2016-09-26
    • PAIN THERAPEUTICS INCZAMLOOT MICHAEL
    • ZAMLOOT MICHAELBARBIER REMIFRIEDMANN NADAVSRIRANBHATLA VIJAYWATT SEPHEN
    • A61M11/00A61J1/00A61K9/00A61K31/485
    • A61K9/7084A61K9/14A61K9/7038A61K31/485
    • This invention relates to cocrystals of naloxone and of naltrexone and thier use as opioid antagonists. The cocrystais of the invention include naloxone isonicotinamide cocrystal, naloxone hydrochloride piperazine cocrystal, naltrexone menthol cocrystal, naltrexone thymine cocrystal, naltrexone 2,5-dihydroxybenzoic acid cocrystal, naltrexone salicylic acid cocrystal, naltrexone hydrochloride piperazine cocrystal and naltrexone hydrochloride sulfathiazole cocrystal. A drug-in¬ adhesive transdermal patch con taining the opioid analgesic fentanyl or an analog thereof and a cocrystal of naloxone or naltrexone is disclosed. Also disclosed is a method of treating pain, such as acute, chronic or intermittent pain, by applying a drug-in-adhesive transdermal patch of the invention to the skin of a patient in need thereof. Also disclosed is an improved transdermal patch for administering fentanyl or an analog thereof, or for administering a mu opioid agonist, the improvement wherein the transdermal patch contains a cocrystal of the invention in an abuse limiting amount. The improved transdermal patch may be a drug-in-adhesive transdermal patch or a reservoir transdermal patch.
    • 本发明涉及纳洛酮和纳曲酮的共结晶以及它们作为阿片样物质拮抗剂的用途。 本发明的共晶体包括纳洛酮异烟酰胺共晶体,盐酸纳洛酮哌嗪共晶体,纳曲酮薄荷醇共晶体,纳曲酮胸腺嘧啶共晶体,纳曲酮2,5-二羟基苯甲酸共晶体,纳曲酮水杨酸共晶体,纳曲酮盐酸盐哌嗪共晶体和纳曲酮盐酸盐磺胺噻唑共晶体。 公开了包含阿片样镇痛芬太尼或其类似物和纳络酮或纳曲酮共晶体的药物粘附透皮贴剂。 还公开了通过将本发明的药物粘附型透皮贴剂应用于有需要的患者的皮肤来治疗疼痛(例如急性,慢性或间歇性疼痛)的方法。 还公开了用于施用芬太尼或其类似物或用于施用mu阿片样物质激动剂的改进的透皮贴剂,其中透皮贴剂含有滥用限制量的本发明共结晶。 改进的透皮贴剂可以是药物粘附透皮贴剂或储库透皮贴剂。